Process for preparation of alkenylphosphine oxides or alkenylphosphinic esters

ABSTRACT

A novel process for preparation of alkenylphosphine oxides or alkenylphosphinic acid esters provided by which the objective compounds can be easily, safely and efficiently synthesized and easily separated and purified with little formation of by-products. Specifically, a process of conducting the addition reaction of an easily available secondary phosphine oxide or hydrogen phosphinic acid ester with an acetylene compound with a catalyst containing a Group 9 or 10 metal of the periodic table to thereby obtain the corresponding alkenylphosphine oxide or alkenylphosphinic acid ester.

TECHNICAL FIELD

The present invention relates to a process for the preparation ofalkenylphosphine oxides or alkenylphosphinic acid esters.

These compounds are a group of compounds which are highly useful in viewof synthesis of fine chemicals in such a manner, for instance, they areable to be easily converted to tertiary phosphines and they themselveseasily react with nucleophilic agents and radical species. In addition,they are able to be used for Horner-Witting reaction.

Furthermore, it is known that Alkenylphosphinic acid skeletons are foundin nature and that they themselves exhibit a physiological actionthrough interaction with enzymes, etc.

BACKGROUND OF THE INVENTION

With regard to a method for the synthesis of alkenylphosphine oxides,there have been known a method where an organic metal reagent such as analkenyl Grignard reagent is made to react with a phosphorus halidecompound, a method where secondary phosphine oxide is made to react withan alkenyl halogen compound, etc. However, in the former method, thereis a disadvantage that it is accompanied with production of salt ofmagnesium, etc. while, in the latter method, it is necessary that a baseis added so as to trap the generated hydrogen halide as a salt. Inaddition, both of those methods are not preferred from an industrialview in such a respect that other compounds besides the desired compoundare also formed as by-product.

In the meanwhile, it has been recently found a method where a secondaryphosphine oxide added to an acetylene compound in the presence of apalladium catalyst (Orgnometallics, volume 15, page 3259, 1996; JapanesePatent No. 2,849,712) but selectively of the product is not high in thismethod.

With regard to a method for the synthesis of alkenylphosphinic acidesters through carbon-phosphorus bond forming reaction, the most generalmethod is a substitution reaction of the corresponding alkenyl halidecompound with a hydrogen phosphinic acid ester. However, in this method,it is necessary to add a base for trapping of hydrogen halide which isproduced simultaneously as a result of the reaction whereby largequantities of hydrogen halide salt are produced at the same time. Inaddition, the alkenyl halide compound which is a starting materialtherefor is not always easily available industrially and, further, itusually has toxicity. Therefore, the method is never a method which isindustrially advantageous.

DISCLOSURE OF THE INVENTION

The present invention has been achieved in view of the above-mentionedcurrent status and its object is to provide a novel production processfor alkenylphosphine oxides or alkenylphosphinic acid esters where theproducts can be easily, safely and efficiently synthesized, by-productsare little and separation and purification are easy.

The present inventors have carried out an intensive study for thereaction of an easily-available secondary phosphine oxide or hydrogenphosphinic acid ester with an acetylene compound and, as a result, theyhave found that the addition reaction proceeds in the presence of aspecific catalyst giving the corresponding alkenylphosphine oxide oralkenylphosphinic acid ester easily. On the basis of such a fact, thepresent invention has been accomplished.

Thus, in accordance with the present invention, there is provided aprocess for the production of an alkenylphosphine oxide compound (whenR₀ ⁴ is R⁴) and alkenylphosphinic acid ester compound (when R₀ ⁴ is OR⁴)represented by the formula [III]R¹{CH═CR²[P(O)(R³)(R₀ ⁴)]}_(n)  [III]and/or the formula [IV]R¹{C[P(O)(R³)(R₀ ⁴)]═CHR²}_(n)  [IV](R¹, R², R³ and R₀ ⁴ are the same as those defined below), characterizedin that, a catalyst containing a metal of group 9 or group 10 of theperiodic table is used and an acetylene compound represented by theformula [I]R¹(C≡CR²)_(n)  [I](in the formula, n is 1 or 2; R¹ and R² each when n is 1 and R² when nis 2 is hydrogen atom, an optionally substituted alkyl group, anoptionally substituted cycloalkyl group, an optionally substitutedalkenyl group, an optionally substituted cycloalkenyl group, anoptionally substituted aryl group, an optionally substituted aralkylgroup, an optionally substituted aryloxy group, an optionallysubstituted heteroaryl group, a ferrocenyl group, an optionallysubstituted alkoxy group or an optionally substituted silyl group; andR¹ when n is 2 is an optionally substituted alkylene group, anoptionally substituted cycloalkylene group, an optionally substitutedalkenylene group, an optionally substituted cycloalkenylene group, anoptionally substituted arylene group, an optionally substitutedaralkylene group, an optionally substituted arylenedioxy group, anoptionally substituted heteroarylene group, a ferrocenylene group, anoptionally substituted alkylenedioxy group or an optionally substitutedsilylenedioxy group) is made to react with a compound represented by theformula [II]HP(O)(R³)(R₀ ⁴)  [II][in the formula, R³ is an alkyl group, a cycloalkyl group, an aralkylgroup or an aryl group; and R₀ ⁴ is R⁴ or OR⁴ (where R⁴ is an alkylgroup, a cycloalkyl group, an aralkyl group or an aryl group)].

BEST MODE FOR CARRYING OUT THE INVENTION

In the production process according to the present invention, theacetylene compound used as a starting material is represented by theabove-mentioned [I] where R¹ and R² each when n is 1 and R² when n is 2is hydrogen atom, an optionally substituted alkyl group, an optionallysubstituted cycloalkyl group, an optionally substituted alkenyl group,an optionally substituted cycloalkenyl group, an optionally substitutedaryl group, an optionally substituted aralkyl group, an optionallysubstituted aryloxy group, an optionally substituted heteroaryl group, aferrocenyl group, an optionally substituted alkoxy group or anoptionally substituted silyl group.

With regard to the alkyl group when R¹ and/or R² in the formula [I], theformula [III] and the formula [IV] are/is optionally substitutedalkyl(s), there may be exemplified a straight-chain or branched alkylgroup having 1˜20, preferably 1˜10 or, more preferably, 1˜6 carbon(s).To be more specific, methyl group, ethyl group, propyl group, isopropylgroup, butyl group, isobutyl group, sec-butyl group, tert-butyl group,pentyl group, hexyl group, etc. may be exemplified.

With regard to a cycloalkyl group of the optionally substitutedcycloalkyl group, there may be exemplified a monocyclic, polycyclic orfused-ring cycloalkyl group having 3˜30, preferably 3˜20 or, morepreferably, 3˜10 carbons. To be more specific, cyclopropyl group,cyclopentyl group, cyclohexyl group, cyclooctyl group, etc. may beexemplified.

With regard to an alkenyl group of the optionally substituted alkenylgroup, there may be exemplified a group where the above-mentioned alkylgroup having 2 or more carbons has one or more unsaturated groups suchas a double bond. To be more specific, vinyl group, allyl group,1-propenyl group, isopropenyl group, 2-butenyl group, 1,3-butadienylgroup, 2-pentenyl group, 2-hexenyl group, etc. may be exemplified.

With regard to a cycloalkenyl group of the optionally substitutedcycloalkenyl group, there may be exemplified a group where theabove-mentioned cycloalkyl group has one or more unsaturated group(s)such as double bond. To be more specific, cyclopropenyl group,cyclopentenyl group, cyclohexenyl group, etc. may be exemplified.

With regard to an aryl group of the optionally substituted aryl group,there may be exemplified a monocyclic, polycyclic or fused-ring aromatichydrocarbon group having 6˜30, preferably 6˜20 or, more preferably, 6˜14carbons. To be more specific, phenyl group, tolyl group, xylyl group,naphthyl group, methylnaphthyl group, anthryl group, phenanthryl group,biphenyl group, etc. may be exemplified.

With regard to an aralkyl group of the optionally substituted aralkylgroup, there maybe exemplified a monocyclic, polycyclic or fused-ringaralkyl group having 7˜30, preferably 7˜20 or, more preferably, 7˜15carbons. To be more specific, benzyl group, phenethyl group,naphthylmethyl group, naphthylethyl group, etc. may be exemplified.

With regard to an aryloxy group of the optionally substituted aryloxygroup, there may be exemplified an aryloxy group having a monocyclic,polycyclic or fused-ring aromatic hydrocarbon group having 6˜30,preferably 6˜20 or, more preferably, 6˜14 carbons. To be more specific,phenoxy group, tolyloxy group, xylyloxy group, naphthoxy group,methylnaphthyloxy group, anthryloxy group, phenanthryloxy group,biphenyloxy group, etc. may be exemplified.

With regard to a heteroaryl group of the optionally substitutedheteroaryl group, there maybe exemplified various kinds ofheteroaromatic ring groups containing hetero atoms such as oxygen,nitrogen and sulfur and numbers of carbons contained therein are usually4˜12 and, preferably, 4˜8. Specific examples thereof are thienyl group,furyl group, pyridyl group and pyrrolyl group.

With regard to an alkoxy group of the optionally substituted alkoxygroup, there may be exemplified an alkoxy group having 1˜8 or,preferably, 1˜4 carbon(s) and specific examples thereof are methoxygroup, ethoxy group and butoxy group.

With regard to a substituent for those alkyl group, cycloalkyl group,alkenyl group, cycloalkenyl group, aryl group, aralkyl group, aryloxygroup, heteroaryl group and alkoxy group, there may be exemplified analkyl group; hydroxyl group; an alkoxy group such as methoxy group,ethoxy group, propoxy group and butoxy group; a halogen atom such aschlorine, bromine and fluorine; cyano group; a dialkylamino group suchas dimethylamino group and diethylamino group; an alkoxycarbonyl groupsuch as methoxycarbonyl group and ethoxycarbonyl group; silyl group; asubstituted silyl group such as trimethylsilyl group, triethylsilylgroup, tert-butyldimethylsilyl group and triphenylsilyl group; and asiloxy group such as tert-butyldimethylsiloxy group.

With regard to a silyl group of the optionally substituted silyl group,that which is substituted, for example, with alkyl, aryl, aralkyl andalkoxy groups may be covered as well. Specific examples thereof aretrimethylsilyl group, triethylsilyl group, triphenylsilyl group,phenyldimethylsilyl group, trimethoxysilyl group andtert-butyldimethylsilyl group.

The optionally substituted alkylene group, the optionally substitutedcycloalkylene group, the optionally substituted alkenylene group, theoptionally substituted cycloalkenylene group, the optionally substitutedarylene group, the optionally substituted aralkylene group, theoptionally substituted arylenedioxy group, the optionally substitutedheteroarylene group, the ferrocenylene group, the optionally substitutedalkylenedioxy group or the optionally substituted silylenedioxy grouprepresented by R¹ in case n is 2 is selected from a divalent residuewhere one hydrogen atom is removed from the already-mentioned R¹ when nis 1 or a divalent residue where one hydrogen atom is substituted withone oxygen atom in the R¹ and specific examples thereof are methylenegroup, ethylene group, trimethylene group, methylethylene group,propylene group, tetramethylene group, 1,2-dimethylethylene group,pentamethylene group, hexamethylene group, cyclohexylene group,phenylene group, naphthylene group, furandiyl group, ferrocenylenegroup, 2-butenediyl group, tetramethylenedioxy group, phenylenedioxygroup and dimethylsilylene group.

Examples of the acetylene compound which is preferably used in theproduction process of the present invention are unsubstituted acetylene,methylacetylene, butyne, 1-hexyne, 2-hexyne, 1-octyne, 4-octyne,1-butyn-4-ol, 2-butyn-1-ol, 3-butyn-1-ol, 5-hexyn-1-ol, 1-octyn-3-ol,5-chloro-1-pentyne, phenylacetylene, trimethylsilylacetylene,ethynylthiophene, hexynonitrile, cyclohexenylacetylene,ethynylferrocene, 1,4-pentadiyne, 1,8-nonadiyne and diethynylbenzenealthough they are non-limitative.

The secondary phosphine oxide or hydrogen phosphinic acid ester used asa starting material in the production process of the present inventionis represented by the already-mentioned formula [II]. In the formula, R³and R⁴ each independently is an alkyl group, a cycloalkyl group, anaralkyl group or an aryl group.

With regard to the alkyl group, the cycloalkyl group, the aralkyl groupor the aryl group represented by R³ and R⁴ in the formulae [II], [III]and [IV], the same ones as those listed in the above passage for R¹ andR² may be exemplified.

Specific examples of the preferred secondary phosphine oxide arediphenylphosphine oxide, etc. Specific examples of the preferredhydrogen phosphinic acid ester are ethyl phenylphosphinate andcyclohexyl phenylphosphinate although they are non-limitative.

Ratio of the acetylene compound to the secondary phosphine oxidecompound or the hydrogen phosphinic acid ester compound used is usuallypreferred to be 1:1 in terms of their molar ratio although occurrence ofthe reaction is not inhibited even when the ratio is smaller or largerthan that.

In order to carry out the reaction of the present invention, it ispreferred to use a catalyst containing metal of group 9 or group 10 ofthe periodic table and it is possible to use a single substancecontaining palladium or rhodium or a catalyst where such a metal iscarried on activated charcoal, silica or the like. It is also possibleto use a complex catalyst containing rhodium or palladium. With regardto such a complex catalyst, although that of various structures may beused, preferred ones are those having the so-called low valence andthose which have tertiary phosphine or tertiary phosphite as a ligandare preferred embodiments as well. It is also a preferred embodiment touse a precursor which is easily converted to a low valence in thereaction system. Further, a process where a complex containing neithertertiary phosphine nor tertiary phosphite as a ligand is mixed withtertiary phosphine or phosphite in the reaction system to form a lowvalence complex having tertiary phosphine or phosphite as a ligand inthe reaction system is a preferred embodiment as well. With regard to aligand which achieves an advantageous efficiency in any of thosemethods, there may be exemplified various tertiary phosphines andtertiary phosphites.

Examples of the ligand which can be preferably used in the presentinvention are triphenylphosphine, diphenylmethylphosphine,phenyldimethylphosphine, 1,4-bis(diphenylphosphino)butane,1,3-bis(diphenylphosphino)propane, 1,2-bis(diphenylphosphino)ethane,1,1′-bis(diphenylphosphino)ferrocene, trimethyl phosphite and triphenylphosphite.

With regard to the complex containing neither tertiary phosphine nortertiary phosphite which is used together therewith, there may beexemplified acetylacetonatobis(ethylene)rhodium, achlorobis(ethylene)rhodium dimer, dicarbonyl(acetylacetonato)rhodium,hexarhodiumhexadecacarbonyl, chloro(1,5-cyclooctadiene)rhodium dimer, achloro(norbornadiene)rhodium dimer, bis(dibenzylideneacetone)palladiumand palladium acetate although they are non-limitative.

With regard to the preferably used phosphine or phosphite complex, theremay be exemplified chlorocarbonylbis(triphenylphosphine)rhodium,hydridecarbonyltris(triphenylphosphine)rhodium,chlorotris(triphenylphosphine)rhodium,bromotris(triphenylphosphine)rhodium,chlorocarbonylbis(triphenylphosphite)rhodium,dimethylbis(triphenylphosphine)palladium,dimethylbis(diphenylmethylphosphine)palladium,dimethylbis(dimethylphenylphosphine)palladium,dimethylbis(triethylphosphine)palladium,(ethylene)bis(triphenylphosphine)palladium,tetrakis(triphenylphosphine)palladium anddichlorobis(triphenylphosphine)palladium.

In order to carry out the reaction of the present invention for theproduction of alkenylphosphine oxide, it is particularly preferred touse a rhodium catalyst.

With regard to the rhodium catalyst, it is possible to use that ofvarious structures such as metallic rhodium species and rhodiumcompound.

With regard to the metallic rhodium species, there may be exemplifiedrhodium black, rhodium powder and rhodium which is carried on a carriersuch as rhodium carried on alumina, rhodium carried on silica andrhodium carried on activated carbon.

With regard to the rhodium compound, there may be used any of compoundsof mono- to trivalent rhodium and any of complex containing no ligandand complex where ligand such as tertiary phosphine and tertiaryphosphite is coordinated thereto. Examples thereof are rhodium saltssuch as a rhodium acetate dimer, rhodiumhalide (such as rhodiumchloride, rhodium bromide and rhodium iodide) and rhodiumacetylacetonate, organorhodium compounds such asacetylacetonatobis(ethylene)rhodium, a chlorobis(ethylene)rhodium dimer,dicarbonyl(acetylacetonato)rhodium, hexarhodiumhexadecacarbonyl,chloro(1,5-cyclooctadiene)rhodium dimer, chloro(norbornadiene)rhodiumdimer and chloro(1,5-hexadiene)rhodium dimmer, and rhodium complexessuch as chlorocarbonylbis(triphenylphosphine)rhodium,hydridocarbonyltris(triphenylphosphine)rhodium,chlorotris(triphenylphosphine)rhodium,bromotris(triphenylphosphine)rhodium,iodotris(triphenylphosphine)rhodium, chlorocarbonylbis(trimethylphosphite)rhodium, bromotris(triphenylphosphine)rhodium,chloro(1,5-cyclooctadienyl)(triphenylphosphine)rhodium andtrichlorotris(pyridine)rhodium although they are non-limitative.

A method where a rhodium complex containing neither tertiary phosphinenor tertiary phosphite is used together with tertiary phosphine ortertiary phosphite to generate a rhodium complex having tertiaryphosphine or tertiary phosphite in the reaction system, and to use theresulting rhodium species as a catalyst is a preferred embodiment aswell.

Further, a method where a rhodium complex which is formed in a reactionsystem wherein a base such as amine is added to a rhodium complexcontaining no ligand is used as a catalyst is a preferred embodiment aswell.

In order to efficiently carry out the reaction of the present inventionfor the production of the alkenylphosphinic acid ester compound, acomplex catalyst of low valence is preferred and a complex catalyst oflow valence containing rhodium or palladium where tertiary phosphine ortertiary phosphite is a ligand is particularly preferred. It is also apreferred embodiment to use a precursor which is easily converted to lowvalence in the reaction system. Further, it is also a preferredembodiment that, in the reaction system, a complex containing neithertertiary phosphine nor tertiary phosphite is mixed with a tertiaryphosphine or phosphite and a low valence complex where tertiaryphosphine or phosphite is a ligand is formed in the reaction system.

In the reaction of the present invention where alkenylphosphinic acidester compounds are produced, palladium catalyst, rhodium catalyst, etc.show the activity even when used alone although it is also possible touse together with a phosphinic acid additive. In particular, in thereaction where regioisomers are produced, regioselectivity becomes highby the joint use with a phosphinic acid additive and, therefore, it ispreferred to use jointly in such a case. Such a phosphinic acid isrepresented, for example, by the formula [V].HO—P(O)(R⁵)₂  [V]

(In the formula, R⁵ is an alkyl group, a cycloalkyl group or an arylgroup.)

In the formula [V] where R⁵ is an alkyl group, examples of the alkylgroup are alkyl groups having 1˜6 or, preferably, 1˜4 carbon(s).Specific examples thereof are methyl, ethyl, n- or isopropyl group, n-,iso-, sec- or tert-butyl group, n-pentyl group and n-hexyl group.

When it is a cycloalkyl group, examples of the cycloalkyl group arecycloalkyl groups having 3˜12 or, preferably, 5˜6 carbons and specificexamples thereof are cyclopentyl group and cyclohexyl group.

When it is an aryl group, examples of the aryl group are aryl groupshaving 6˜14 or, preferably, 6˜10 carbons. Specific examples thereof arephenyl group and naphthyl group and there are also included substitutedgroups thereof (such as tolyl group, xylyl group and benzylphenylgroup).

The alkyl, cycloalkyl or aryl group represented by R⁵ may be substitutedwith a functional group which is inert to the reaction, such as methoxygroup, methoxycarbonyl group, cyano group, dimethylamino group, fluorogroup, chloro group and hydroxyl group.

Specific examples of the phosphinic acid used in the present inventionare diphenylphosphinic acid and dimethylphosphinic acid. The amount ofphosphinic acid relative to the hydrogen phosphinic acid ester used isequimolar or less or, preferably, 0.1˜10 molar %.

With regard to the above-mentioned catalysts used in the reaction of thepresent invention, one or more thereof is/are appropriately selected andused depending upon the reaction.

The amount of such a catalyst used may be a so-called catalytic amount.Generally, the amount relative to the acetylene compound is 20 molar %or less and, usually, 5 molar % or less is sufficient.

Molar ratio of the acetylene compound or the diacetylene compound to thesecondary phosphine oxide or the hydrogen phosphinic acidester in thereaction is not particularly limited but is usually 1:1 although theoccurrence of the reaction is not disturbed even when the ratio is moreor is less than that.

Although there is no particular need of using a solvent in the reactionof the present invention, it is also possible to carry out the reactionin a solvent if necessary. With regard to the solvent, there may be usedvarious ones such as hydrocarbons, halogenated hydrocarbons, ethers,ketones, nitrites and esters. Each of them may be used solely or two ormore thereof may be used as a mixture thereof.

With regard to the reaction temperature, the reaction does not proceedat an advantageous rate when it is too low while, when it is too high,the catalyst decomposes. Therefore, it is generally selected from therange of −20° C.˜300° C. and, preferably, it is carried out within arange of from room temperature to 150° C.

The catalyst used in the present invention is sensitive to oxygen and itis preferred to carry out the reaction in an atmosphere of inert gassuch as nitrogen, argon or methane. Separation of the product from thereaction mixture can be easily achieved by means of chromatography,distillation, recrystallization, etc.

The present invention will now be more specifically illustrated by wayof the following Examples although the present invention is not limitedby those Examples at all.

EXAMPLES Example 1

To 1 ml of toluene were added 1 mmol of diphenylphosphine oxide, 1 mmolof 1-octyne and 3 molar % of RhCl(PPh₃)₃ as a catalyst followed bysubjecting to a reaction in a nitrogen atmosphere at room temperaturefor 1 hour. The reaction solution is concentrated and then isolated andpurified by means of liquid chromatography to give[(E)-1-octen-1-yl]diphenylphosphine oxide in a yield of 70%.

This compound is a known compound and its structure was determined bymeans of comparison with an authentic sample which was separatelysynthesized.

Example 2

The reaction was carried out under the same conditions as in Example 1using an RhBr(PPh₃)₃ catalyst whereupon, after 1 hour, the product[(E)-1-octen-1-yl]diphenylphosphine oxide was obtained in a yield of95%.

Example 3

The reaction was carried out under the same conditions as in Example 1using an RhI(PPh₃)₃ catalyst whereupon, after 1 hour, the product[(E)-1-octen-1-yl]diphenylphosphine oxide was obtained in a yield of100%.

Example 4

The reaction was carried out under the same conditions as in Example 1using an RhCl(CO)(PPh₃)₂ catalyst at 80° C. whereupon, after 0.5 hour,the product [(E)-1-octen-1-yl]diphenylphosphine oxide was obtained in ayield of 89%.

Example 5

The reaction was carried out under the same conditions as in Example 1using an RhH(CO)(PPh₃)₃ catalyst at 80° C. whereupon, after 0.5 hour,the product [(E)-1-octen-1-yl]diphenylphosphine oxide was obtained in ayield of 87%.

Example 6

The reaction was carried out under the same conditions as in Example 1using an RhCl(cod)₂ catalyst at room temperature whereupon, after 1hour, the product [(E)-1-octen-1-yl]diphenylphosphine oxide was obtainedin a yield of 65%.

Example 7

The reaction was carried out under the same conditions as in Example 1using a dicarbonyl(acetylacetonato)rhodium (I) catalyst at 80° C.whereupon, after 1.5 hours, the product[(E)-1-octen-1-yl]diphenylphosphine oxide was obtained in a yield of32%.

Example 8

The reaction was carried out under the same conditions as in Example 1using an ethylene(acetylacetonato)rhodium (I) catalyst at 80° C.whereupon, after 1.5 hours, the product[(E)-1-octen-1-yl]diphenylphosphine oxide was obtained in a yield of67%.

Example 9

The reaction was carried out under the same conditions as in Example 1using an [Rh(OAc)₂]₂ catalyst at 80° C. whereupon, after 1.5 hours, theproduct [(E)-1-octen-1-yl]diphenylphosphine oxide was obtained in ayield of 12%.

Example 10

The reaction was carried out under the same conditions as in Example 1using a rhodium chloride catalyst by addition of 2 ml of ethanol and 4mmol of triethylamine at 80° C. whereupon, after 3 hours, the product[(E)-1-octen-1-yl]diphenylphosphine oxide was obtained in a yield of97%.

Example 11

The reaction was carried out under the same conditions as in Example 1using rhodium carried on activated carbon (5% rhodium being carried) at110° C. whereupon, after 7 hours, the product[(E)-1-octen-1-yl]diphenylphosphine oxide was obtained in a yield of91%.

Examples 12˜25

Various kinds of alkenylphosphine oxides were synthesized using variousacetylene compounds by the same means as in Example 1. The result issummarized in Table 1.

TABLE 1 Examples Acetylene Products Yields (%) 12

93 13

89 14

88 15

92 16

86 17

87 18

94 19

85 20

81 21

92 22

93 23

94 24

76 25

91

Example 26

To 2 ml of toluene under a nitrogen atmosphere were added 10 molar % ofdiphenylphosphinic acid, 1 mmol of ethyl phenylphosphinate, 1 mmol of1-octyne and 5 molar % of Me₂Pd(PPhMe₂)₂ as a catalyst and the mixturewas subjected to a reaction at 80° C. for 5 hours to give a mixture ofethyl phenyl[(E)-1-octen-1-yl]phosphinate and ethylphenyl(1-octen-2-yl)phosphinate (ratio=4:96) in a yield of 96%.

The latter compound is a novel compound which has not been mentioned inliteratures. The spectral data of ethyl phenyl(1-octen-2-yl)phosphinateare as follows.

¹H NMR (500 MHz, CDCl₃) δ 7.69˜7.73 (m, 2H), 7.45˜7.46 (m, 1H),7.39˜7.41 (m, 2H), 5.91 (dd, 1H, J_(HP)=21.4 Hz, J=1.2 Hz), 5.71 (dd,1H, J_(HP)=44.0 Hz, J=1.2 Hz), 3.93˜4.04 (m, 2H), 2.10˜2.13 (m, 2H),1.34˜1.36 (m, 2H), 1.28 (t, 3H, J=7.0 Hz), 1.13˜1.19 (m, 4H), 0.77 (t,3H, J=7.0 Hz).

¹³C NMR (125.4 MHz, CDCl₃) δ 142.78(J_(CP)=121.9 Hz), 132.12, 131.83,130.73 (J_(CP)=131.2 Hz), 128.47, 128.08, 60.80, 31.56, 31.43, 28.80,27.91, 22.54, 16.51, 14.04.

³¹P NMR (201.9 MHz), CDCl₃) δ 33.26.

HRMS as C₁₆H₂₅O₂P, calculated: 280.1592, found: 280.1581.

Example 27

In toluene (2 ml)under a nitrogen atmosphere at 100° C. for 20 hours, 1mmol of cyclohexyl phenylphosphinate and 1 mmol of 1-octene were allowedto react using 3 molar % of Rh(PPh₃)₃Br as a catalyst to give cyclohexylphenyl[(E)-1-octen-1-yl]phosphinate in a yield of 98%.

Example 28

The reaction of Example 26 was carried out without addition ofdiphenylphosphinic acid and, as a result, a mixture (ratio=44:56) ofethyl phenyl[(E)-1-octen-1-yl]phosphinate and ethylphenyl(1-octen-2-yl)phosphinate was obtained in a yield of 71%.

Examples 29˜38

Various kinds of alkenylphosphinic acid esters were synthesized by thesame means as in Example 26 using various acetylene compounds. Theresult is summarized in Table 2.

TABLE 2 Examples Alkynes Adducts Yields (%) 29 ≡

76 30

99 31

95 32

93 33

95 34

91 35

77 36

63 37

85 38

99

INDUSTRIAL APPLICABILITY

The present invention provides a process for the production ofalkenylphosphine oxide compounds or alkenylphosphinic acid estercompounds which are useful as intermediates for the synthesis ofphysiologically active substances such as pharmaceuticals andagricultural chemicals, ligands for the preparation of catalysts, etc.in a high yield and a high utility. In accordance with the process forproduction according to the present invention, it is possible to easily,safely and efficiently synthesize the aimed alkenylphosphine oxidecompounds or alkenylphosphinic acid esters by the reaction of acetylenesmerely with phosphine oxide or hydrogen phosphinic acid ester andseparation and purification of the product are easy as well.Accordingly, the present invention results in a great effect inindustry.

1. A process for the production of compound(s) represented by theformula [III]R¹{CH═CR²[P(O)(R³)(R₀ ⁴)]}_(n)  [III] and/or the formula [IV]R¹{C[P(O)(R³)(R₀ ⁴)]═CHR²}_(n)  [IV] (R¹, R², R³ and R₀ ⁴ are the sameas those defined below), characterized in that, a catalyst containing ametal of group 9 or group 10 of the periodic table is used and anacetylene compound represented by the formula [I]R¹(C≡CR²)_(n)  [I] (in the formula, n is 1 or 2; R¹ and R² each when nis 1 and R² when n is 2 is hydrogen atom, an optionally substitutedalkyl group, an optionally substituted cycloalkyl group, an optionallysubstituted alkenyl group, an optionally substituted cycloalkenyl group,an optionally substituted aryl group, an optionally substituted aralkylgroup, an optionally substituted aryloxy group, an optionallysubstituted heteroaryl group, a ferrocenyl group, an optionallysubstituted alkoxy group or an optionally substituted silyl group; andR¹ when n is 2 is an optionally substituted alkylene group, anoptionally substituted cycloalkylene group, an optionally substitutedalkenylene group, an optionally substituted cycloalkenylene group, anoptionally substituted arylene group, an optionally substitutedaralkylene group, an optionally substituted arylenedioxy group, anoptionally substituted heteroarylene group, a ferrocenylene group, anoptionally substituted alkylenedioxy group or an optionally substitutedsilylenedioxy group) is made to react with a compound represented by theformula [II]HP(O)(R³)(R₀ ⁴)  [II] [in the formula, R³ is an alkyl group, acycloalkyl group, an aralkyl group or an aryl group and R₀ ⁴ is R⁴ orOR⁴ (where R⁴ is an alkyl group, a cycloalkyl group, an aralkyl group oran aryl group)].
 2. The process for the production according to claim 1,wherein R₀ ⁴ in the formula [II], the formula [III] and the formula [IV]is R⁴.
 3. The process for the production according to claim 2, whereinthe metal of group 9 or group 10 of the periodic table is rhodium. 4.The process for the production according to claim 3, wherein thecatalyst containing rhodium is a metallic rhodium species.
 5. Theprocess for the production according to claim 4, wherein the metallicrhodium species is rhodium black, rhodium powder or rhodium which iscarried on a carrier.
 6. The process for the production according toclaim 3, wherein the catalyst containing rhodium is a rhodium complexcatalyst.
 7. The process for the production according to claim 6,wherein the rhodium complex catalyst is a complex catalyst containing noligand.
 8. The process for the production according to claim 6, whereinthe rhodium complex catalyst is a rhodium complex catalyst in whichtertiary phosphine or tertiary phosphite is a ligand.
 9. The process forthe production according to claim 6, wherein the rhodium complexcatalyst is a precursor complex which is easily able to be converted toa low valence complex in a reaction system.
 10. The process for theproduction according to claim 6, wherein the rhodium complex catalyst isa rhodium complex catalyst where tertiary phosphine and/or tertiaryphosphite as ligand(s) which is formed in a reaction system using arhodium complex containing neither tertiary phosphine nor tertiaryphosphite as a ligand together with a tertiary phosphine and/or tertiaryphosphite.
 11. The process for the production according to claim 1,wherein R₀ ⁴ in the formula [II], the formula [III] and the formula [IV]is OR⁴.
 12. The process for the production according to claim 11,wherein the metal of group 9 is rhodium.
 13. The process for theproduction according to claim 11, wherein the metal of group 10 ispalladium.
 14. The process for the production according to claim 11,wherein the catalyst containing the metal of group 9 or group 10 of theperiodic table is a low valence complex catalyst.
 15. The process forthe production according to claim 11, wherein the catalyst containingthe metal of group 9 or group 10 of the periodic table is a low valencecomplex catalyst where tertiary phosphine or tertiary phosphite as aligand.
 16. The process for the production according to claim 11,wherein the catalyst containing the metal of group 9 or group 10 of theperiodic table is a precursor complex which is able to be easilyconverted to a low valence in a reaction system.
 17. The process for theproduction according to claim 11, wherein the catalyst containing themetal of group 9 or group 10 of the periodic table is a low valencecomplex where tertiary phosphine and/or tertiary phosphite as ligand(s)which is formed in are action system using the metal complex containingneither tertiary phosphine nor tertiary phosphite as a ligand togetherwith a tertiary phosphine and/or tertiary phosphite.
 18. The process forthe production according to any of claims 11 to 17, wherein the reactionis carried out in the presence of a phosphinic acid represented by theformula [V]HO—P(O)(R⁵)₂  [V] (in the formula, R⁵ is an alkyl group, a cycloalkylgroup or an aryl group).